Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three-to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged >50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P ‫؍‬ 0.001 and P ‫؍‬ 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients >50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.Herpes zoster remains an important medical problem throughout the world. The characteristic rash and associated pain occur when varicella-zoster virus, which becomes dormant in sensory ganglia following primary varicella-zoster virus infection, is reactivated, often in association with declining cellular immunity associated with advancing age (4). Thus, in otherwise healthy adults, the risk of herpes zoster increases with age (12). Pain persisting after rash healing occurs in more than 50% of untreated patients and is the major complication in older adults (3, 13). The pain is often accompanied by abnormal sensations such as allodynia, tingling, or numbness and decreases gradually over several months in most patients (2), although some patients have pain persisting beyond 6 months (8,13,20). Acyclovir (Zovirax) administered orally (800 mg five times daily) is widely used for treatment of acute herpes zoster. It speeds rash healing and decreases the severity of acute pain (14,18,25,28). In some studies, acyclovir also appears to reduce the prevalence, severity, and duration of chronic pain (7,11,14,18). Furthermore, oral acyclovir reduces the prevalence and severity of certain intraocular complications associated with herp...

We developed a clinical score to monitor tuberculosis patients in treatment and to assess clinical outcome. We used the WHO clinical manual to choose signs and symptoms, including cough, haemoptysis, dyspnoea, chest pain, night sweating, anaemia, tachycardia, lung-auscultation finding, fever, low body-mass index, low mid-upper arm circumference giving patients a TBscore from 0 to 13. We validated the score with data from a cohort of 698 TB patients, assessing sensitivity to change and ability to predict mortality. The TBscore declined for 96% of the surviving patients from initiation to end of treatment, and declined with a similar pattern in HIV-infected and HIV-uninfected patients, as well as in smear negative and smear positive patients. The risk of dying during treatment increased with higher TBscore at inclusion. For patients with a TBscore of >8 at inclusion, mortality during the 8 months treatment was 21% (45/218) versus 11% (55/480) for TBscore <8 (p< 0.001). TBscore assessed at end of treatment also strongly predicted subsequent mortality. The TBscore is a simple and low-cost tool for clinical monitoring of tuberculosis patients in low-resource settings and may be used to predict mortality risk. Low TBscore or fall in TBscore at treatment completion may be used as a measure of improvement.

Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Hypovitaminosis D was highly prevalent in TB patients and in healthy controls living at 12 degrees N; severe VDD was rare in TB patients. The finding indicates that the serum 25(OH)D(3) concentration is associated with TB infection, but whether this role is a symptom or is causal was not established.

Overall morbidity and mortality rates in childhood are reported to be higher in males than females. As respiratory tract infections constitute the leading cause of childhood hospitalization, we examined the gender difference in rates of hospitalization due to respiratory tract infections in Danish youth (under age 25). We studied a total of 64,049 hospitalizations for otitis media, pneumonia, influenza, and other acute respiratory tract infections from 1995 to 1999, with calculation of hospitalization rates by age and gender. The male-female hospitalization rate ratio (HRR) for admission due to a respiratory tract infection decreased from 1.45 (95% confidence interval (CI) 1.42-1.48) in the age group 0 - < 5 y, to 1.62 (95% CI 1.55-1.70) in the age group 5 - < 10 y, 1.13 (95% CI 1.04-1.22) in the age group 10 - < 15 y, 0.83 (95% CI 0.76-0.90) in the age group 15 - < 20 y, and 0.87 (95% CI 0.80-0.95) in the age group 20 - < 25 y. In young children, boys were hospitalized more often than girls, but the reverse applied in children and adolescents 15-25 y of age. The study generates the hypothesis that gender plays a role in the susceptibility for respiratory infections in early childhood.

To evaluate Bordetella pertussis as a cause of persistent cough in adults, we examined 201 patients who had a cough for 2-12 weeks and no pulmonary disease. We obtained the following at presentation: medical history, chest radiograph, respiratory function measurement, nasopharyngeal aspirate for polymerase chain reaction (PCR), nasopharyngeal swab specimen for culture, and a blood sample (acute serum). Four weeks later a second blood sample (convalescent serum) was obtained. Control sera were obtained from 164 age-matched healthy blood donors with no history of cough during the previous 12 weeks. Four patients were B. pertussis culture-positive; 11 (including the culture-positive patients) were B. pertussis PCR-positive; and 33, including 10 of the 11 PCR-positive patients, had serological evidence of recent B. pertussis infection. Pertussis-positive and -negative patients could not be discriminated by a history of cough. We conclude that B. pertussis infection is a common cause of persistent cough in adults. This is of concern, because these patients may be B. pertussis reservoirs from which transmission may occur to infants, in whom the disease can be devastating.

Genetic polymorphisms of bovine milk proteins affect the protein profile of the milk and, hence, certain technological properties, such as casein (CN) number and cheese yield. However, reports show that such polymorphisms may also affect the health-related properties of milk. Therefore, to gain insight into their digestion pattern and bioactive potential, β-CN was purified from bovine milk originating from cows homozygous for the variants A(1), A(2), B, and I by a combination of cold storage, ultracentrifugation, and acid precipitation. The purity of the isolated β-CN was determined by HPLC, variants were verified by mass spectrometry, and molar extinction coefficients at λ=280nm were determined. β-Casein from each of the variants was subjected to in vitro digestion using pepsin and pancreatic enzymes. Antioxidant and angiotensin-converting enzyme (ACE) inhibitory capacities of the hydrolysates were assessed at 3 stages of digestion and related to that of the undigested samples. Neither molar extinction coefficients nor overall digestibility varied significantly between these 4 variants; however, clear differences in digestion pattern were indicated by gel electrophoresis. In particular, after 60min of pepsin followed by 5min of pancreatic enzyme digestion, one ≈4kDa peptide with the N-terminal sequence (106)H-K-E-M-P-F-P-K- was absent from β-CN variant B. This is likely a result of the (122)Ser to (122)Arg substitution in variant B introducing a novel trypsin cleavage site, leading to the changed digestion pattern. All investigated β-CN variants exhibited a significant increase in antioxidant capacity upon digestion, as measured by the Trolox-equivalent antioxidant capacity assay. After 60min of pepsin + 120min of pancreatic enzyme digestion, the accumulated increase in antioxidant capacity was ≈1.7-fold for the 4 β-CN variants. The ACE inhibitory capacity was also significantly increased by digestion, with the B variant reaching the highest inhibitory capacity at the end of digestion (60min of pepsin + 120min of pancreatic enzymes), possibly because of the observed alternative digestion pattern. These results demonstrate that genetic polymorphisms affect the digestion pattern and bioactivity of milk proteins. Moreover, their capacity for radical scavenging and ACE inhibition is affected by digestion.

SUMMARYThe concentrations of mannan-binding protein (MBP) in consecutive samples from 10 HIV* persons were estimated using an ELISA based on polyclonal rahbit anti-MBP. The changes in MBP with time were similar in HIV^ and HIV" persons, and did not appear to be of clinical significance. MBP was determined in a further 70 persons found HIV-1 ^ during a period af 25 years (1984)(1985)(1986). Out of the total of 80 patients, 32 have by now died from AIDS. According to the serum level of MBP the HIV-infected persons were grouped into high (>65Qng MBP/ml). intermediate (101-650 ng/ml), and low MBP (< 101 ng/ml). At the termination of the study the frequency of deaths/total in each of the groups were: high MBP, 14/39 (36%); intermediate MBP. 12/26 (46%); and low MBP, 6/14 (43%). There was no association between the MBP level of the individual and the progressive loss of CD4* T cells, and the level of MBP was not predictive for the length of time between the detection of HIV antibodies and development of AIDS, nor for the duration of AIDS before death occurred. The number of HIV ' persons without detectable MBP (10%) was significantly higher than previously reported for healthy persons (2 4%, P = 0 027). The course of HIV infection does not seem to be influenced by the level of MBP. nor does the antimicrobial activity of MBP appear to affect the progression of AIDS. Further studies are required to substantiate the significance of absenee of MBP in the susceptibility to HIV.